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Expert Interview

Slingshot members are talking to an expert! The topic is:

A Second Look at Pliant Therapeutics' bexotegrast and the updated data from the INTEGRIS-PSC Phase 2a trial in primary sclerosing cholangitis (PSC) and biliary fibrosis

Ticker(s): PLRX

Who's the expert?

Institution: Rush University Medical Center

  • Professor of Internal Medicine, Chair of Hepatology, & Associate Director of Solid Organ Transplantation,at Rush University Medical Center.
  • Research interests focus on viral hepatitis – from both a drug development and a clinical perspective - liver transplantation, and complications of chronic liver disease. 
  • Author of the AASLD/IDSA hepatitis C guidance document; Co-chair of the National ALF Medical Advisory Committee and is currently a member of the steering committee for the hepatitis C special interest group for the AASLD.

Interview Questions
Q1.

Reflecting on the INTEGRIS-PSC Phase 2a trial, can you elaborate on the safety profile of PLN-74809 observed over the 12-week period, especially concerning its tolerability in patients with suspected moderate to severe liver fibrosis?

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Q2.

How does the observed reduction in liver fibrosis markers ELF and PRO-C3 with PLN-74809 administration contribute to our understanding of its antifibrotic efficacy in PSC patients?

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Q3.

Based on MRI imaging results from the trial, can you discuss the implications of improved hepatocyte function and bile flow in patients treated with PLN-74809?

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Q4.

In comparison with existing treatment options for PSC, where does PLN-74809 stand in terms of effectiveness and patient outcomes, particularly in light of the trial results?

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Q5.

The trial noted a significant reduction in itch severity with PLN-74809. How important is this finding for the overall quality of life and symptom management in PSC patients?

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Q6.

Considering the varied dosages tested in the trial, how might PLN-74809 enable more personalized treatment strategies for PSC patients?

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Q7.

With the ongoing trial set to continue for a 24-week period, what are your expectations regarding the long-term efficacy and safety of PLN-74809 in PSC treatment?

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Q8.

Following these promising trial results, what are the anticipated next steps in the clinical development and regulatory process for PLN-74809, and how might this influence its accessibility to patients?

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Q9.

How does the use of single nuclei RNA sequencing (snRNA-seq) combined with the precision-cut liver slice (PCLivS) platform enhance our understanding of bexotegrast’s cell-specific effects in treating biliary fibrosis?

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Q10.

The study indicates that bexotegrast had an attenuated effect on immune cell gene expression compared to ALK5i. What are the potential clinical implications of this finding for patients with PSC?

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Q11.

Can you discuss the specific response profiles of key pathologic cell types, such as myofibroblasts and cholangiocytes, to bexotegrast treatment? How does this compare to their response to ALK5i?

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Q12.

What were the most significant differentially expressed genes (DEGs) and pathways identified in the study for bexotegrast-treated cells, and how do these contribute to its antifibrotic effects?

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